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Yin X, Shi Y, Sheng T, Ji C. Early-Life Gut Microbiota: A Possible Link Between Maternal Exposure to Non-Nutritive Sweeteners and Metabolic Syndrome in Offspring. Nutr Rev 2025; 83:e1954-e1969. [PMID: 39348276 DOI: 10.1093/nutrit/nuae140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024] Open
Abstract
Metabolic syndrome (MetS) is recognized as a group of metabolic abnormalities, characterized by clustered interconnected traits that elevate the risks of obesity, cardiovascular and atherosclerotic diseases, hyperlipidemia, and type 2 diabetes mellitus. Non-nutritive sweeteners (NNS) are commonly consumed by those with imbalanced calorie intake, especially in the perinatal period. In the past, accumulating evidence showed the transgenerational and mediated roles of human microbiota in the development of early-life MetS. Maternal exposure to NNS has been recognized as a risk factor for filial metabolic disturbance through various mechanisms, among which gut microbiota and derived metabolites function as nodes linking NNS and MetS in early life. Despite the widespread consumption of NNS, there remain growing concerns about their transgenerational impact on metabolic health. There is growing evidence of NNS being implicated in the development of metabolic abnormalities. Intricate complexities exist and a comprehensive understanding of how the gut microbiota interacts with mechanisms related to maternal NNS intake and disrupts metabolic homeostasis of offspring is critical to realize its full potential in preventing early-life MetS. This review aims to elucidate the effects of early-life gut microbiota and links to maternal NNS exposure and imbalanced offspring metabolic homeostasis and discusses potential perspectives and challenges, which may provide enlightenment and understanding into optimal perinatal nutritional management.
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Affiliation(s)
- Xiaoxiao Yin
- Nanjing Medical Research Center for Women and Children, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu 210004, China
- School of Nursing, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Yujie Shi
- Nanjing Medical Research Center for Women and Children, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu 210004, China
| | - Tongtong Sheng
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Chenbo Ji
- Nanjing Medical Research Center for Women and Children, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu 210004, China
- School of Nursing, Nanjing Medical University, Nanjing, Jiangsu 211166, China
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Wang T, Zhou D, Hong Z. Adipose tissue in older individuals: a contributing factor to sarcopenia. Metabolism 2024; 160:155998. [PMID: 39128607 DOI: 10.1016/j.metabol.2024.155998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 08/13/2024]
Abstract
Sarcopenia is a geriatric syndrome characterized by a functional decline in muscle. The prevalence of sarcopenia increases with natural aging, becoming a serious health problem among elderly individuals. Therefore, understanding the pathology of sarcopenia is critical for inhibiting age-related alterations and promoting health and longevity in elderly individuals. The development of sarcopenia may be influenced by interactions between visceral and subcutaneous adipose tissue and skeletal muscle, particularly under conditions of chronic low-grade inflammation and metabolic dysfunction. This hypothesis is supported by the following observations: (i) accumulation of senescent cells in both adipose tissue and skeletal muscle with age; (ii) gut dysbiosis, characterized by an imbalance in gut microbial communities as the main trigger for inflammation, sarcopenia, and aged adipose tissue; and (iii) microbial dysbiosis, which could impact the onset or progression of a senescent state. Moreover, adipose tissue acts as an endocrine organ, releasing molecules that participate in intricate communication networks between organs. Our discussion focuses on novel adipokines and their role in regulating adipose tissue and muscle, particularly those influenced by aging and obesity, emphasizing their contributions to disease development. On the basis of these findings, we propose that age-related adipose tissue and sarcopenia are disorders characterized by chronic inflammation and metabolic dysregulation. Finally, we explore new potential therapeutic strategies involving specialized proresolving mediator (SPM) G protein-coupled receptor (GPCR) agonists, non-SPM GPCR agonists, transient receptor potential (TRP) channels, antidiabetic drugs in conjunction with probiotics and prebiotics, and compounds designed to target senescent cells and mitigate their pro-inflammatory activity.
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Affiliation(s)
- Tiantian Wang
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
| | - Dong Zhou
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China
| | - Zhen Hong
- Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
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Luzzi A, Briata IM, Di Napoli I, Giugliano S, Di Sabatino A, Rescigno M, Cena H. Prebiotics, probiotics, synbiotics and postbiotics to adolescents in metabolic syndrome. Clin Nutr 2024; 43:1433-1446. [PMID: 38704983 DOI: 10.1016/j.clnu.2024.04.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 12/06/2023] [Accepted: 04/19/2024] [Indexed: 05/07/2024]
Abstract
The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more obesity-related comorbidities. In recent years, emerging evidence supporting the role of gut microbiota in the pathophysiology of metabolic diseases has been reported and the use of prebiotics, probiotics, synbiotics and postbiotics as a strategy to manipulate gut microbiota has become popular. The aim of this review is to explore the relationship between gut microbiota and metabolic syndrome in adolescents and to discuss the potential use of prebiotics, probiotics, synbiotics and postbiotics for the prevention and treatment of this clinical picture in adolescence. According to the most recent literature, prebiotics, probiotics and synbiotics have no clear effect on MetS, but a possible modulation of anthropometric parameters has been observed after synbiotic supplementation. Only one study has examined the role of postbiotics in alleviating metabolic complications in children with obesity but not in adolescents. More extensive research is needed to support the conclusions drawn so far and to develop effective microbiome-based interventions that may help improving the quality of life of children and adolescents exposed to the increasing prevalence of MetS.
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Affiliation(s)
- Alessia Luzzi
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; Post Graduate Course in Food Science and Human Nutrition, Università Statale di Milano, 20122 Milan, Italy; Clinical Nutrition Unit, Department of General Medicine, ICS Maugeri IRCCS, 27100 Pavia, Italy.
| | - Irene Maria Briata
- Post Graduate Course in Food Science and Human Nutrition, Università Statale di Milano, 20122 Milan, Italy; Division of Medical Oncology, E.O. Ospedali Galliera, Genoa, Italy.
| | - Ilaria Di Napoli
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy.
| | - Silvia Giugliano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, 20072, Italy.
| | - Antonio Di Sabatino
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy; First Department of Internal Medicine, Fondazione IRCCS San Matteo, 27100 Pavia, Italy.
| | - Maria Rescigno
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, 20072, Italy; IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy.
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; Clinical Nutrition Unit, Department of General Medicine, ICS Maugeri IRCCS, 27100 Pavia, Italy.
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Gaire TN, Scott HM, Noyes NR, Ericsson AC, Tokach MD, William H, Menegat MB, Vinasco J, Nagaraja TG, Volkova VV. Temporal dynamics of the fecal microbiome in female pigs from early life through estrus, parturition, and weaning of the first litter of piglets. Anim Microbiome 2024; 6:7. [PMID: 38383422 PMCID: PMC10882843 DOI: 10.1186/s42523-024-00294-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 02/07/2024] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND Age-associated changes in the gastrointestinal microbiome of young pigs have been robustly described; however, the temporal dynamics of the fecal microbiome of the female pig from early life to first parity are not well understood. Our objective was to describe microbiome and antimicrobial resistance dynamics of the fecal microbiome of breeding sows from early life through estrus, parturition and weaning of the first litter of piglets (i.e., from 3 to 53 weeks of age). RESULTS Our analysis revealed that fecal bacterial populations in developing gilts undergo changes consistent with major maturation milestones. As the pigs progressed towards first estrus, the fecal bacteriome shifted from Rikenellaceae RC9 gut group- and UCG-002-dominated enterotypes to Treponema- and Clostridium sensu stricto 1-dominated enterotypes. After first estrus, the fecal bacteriome stabilized, with minimal changes in enterotype transition and associated microbial diversity from estrus to parturition and subsequent weaning of first litter piglets. Unlike bacterial communities, fecal fungal communities exhibited low diversity with high inter- and intra-pig variability and an increased relative abundance of certain taxa at parturition, including Candida spp. Counts of resistant fecal bacteria also fluctuated over time, and were highest in early life and subsequently abated as the pigs progressed to adulthood. CONCLUSIONS This study provides insights into how the fecal microbial community and antimicrobial resistance in female pigs change from three weeks of age throughout their first breeding lifetime. The fecal bacteriome enterotypes and diversity are found to be age-driven and established by the time of first estrus, with minimal changes observed during subsequent physiological stages, such as parturition and lactation, when compared to the earlier age-related shifts. The use of pigs as a model for humans is well-established, however, further studies are needed to understand how our results compare to the human microbiome dynamics. Our findings suggest that the fecal microbiome exhibited consistent changes across individual pigs and became more diverse with age, which is a beneficial characteristic for an animal model system.
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Affiliation(s)
- Tara N Gaire
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA
| | - H Morgan Scott
- Department of Veterinary Pathobiology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Noelle R Noyes
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA
| | - Aaron C Ericsson
- Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA
| | - Michael D Tokach
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS, 66506, USA
| | - Hayden William
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS, 66506, USA
| | - Mariana B Menegat
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS, 66506, USA
| | - Javier Vinasco
- Department of Veterinary Pathobiology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - T G Nagaraja
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
| | - Victoriya V Volkova
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA
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Gou H, Song H, Tian Z, Liu Y. Prediction models for children/adolescents with obesity/overweight: A systematic review and meta-analysis. Prev Med 2024; 179:107823. [PMID: 38103795 DOI: 10.1016/j.ypmed.2023.107823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 11/12/2023] [Accepted: 12/11/2023] [Indexed: 12/19/2023]
Abstract
The incidence of obesity and overweight in children and adolescents is increasing worldwide and becomes a global health concern. This study aims to evaluate the accuracy of available prediction models in early identification of obesity and overweight in general children or adolescents and identify predictive factors for the models, thus provide a reference for subsequent development of risk prediction tools for obesity and overweight in children or adolescents. Related publications were obtained from several databases such as PubMed, Embase, Cochrane Library, and Web of Science from their inception to September 18th, 2022. The novel Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed to assess the bias risk of the included studies. R4.2.0 and Stata15.1 softwares were used to conduct meta-analysis. This study involved 45 cross-sectional and/or prospective studies with 126 models. Meta-analyses showed that the overall pooled index of concordance (c-index) of prediction models for children/adolescents with obesity and overweight in the training set was 0.769 (95% CI 0.754-0.785) and 0.835(95% CI 0.792-0.879), respectively. Additionally, a large number of predictors were found to be related to children's lifestyles, such as sleep duration, sleep quality, and eating speed. In conclusions, prediction models can be employed to predict obesity/overweight in children and adolescents. Most predictors are controllable factors and are associated with lifestyle. Therefore, the prediction model serves as an excellent tool to formulate effective strategies for combating obesity/overweight in pediatric patients.
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Affiliation(s)
- Hao Gou
- Department of Pediatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Huiling Song
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Zhiqing Tian
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Yan Liu
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China.
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Turunen J, Tejesvi MV, Paalanne N, Pokka T, Amatya SB, Mishra S, Kaisanlahti A, Reunanen J, Tapiainen T. Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study. Pediatr Res 2024; 95:135-145. [PMID: 37591927 PMCID: PMC10798900 DOI: 10.1038/s41390-023-02783-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 06/30/2023] [Accepted: 07/29/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND The first-pass meconium has been suggested as a proxy for the fetal gut microbiota because it is formed in utero. This systematic review and cohort study investigated how pre- and perinatal factors influence the composition of the meconium microbiota. METHODS We performed the systematic review using Covidence by searching PubMed, Scopus, and Web of Science databases with the search terms "meconium microbiome" and "meconium microbiota". In the cohort study, we performed 16 S rRNA gene sequencing on 393 meconium samples and analyzed the sequencing data using QIIME2. RESULTS Our systematic review identified 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition in relation to subsequent health of infants but gave only limited comparative evidence regarding factors related to the composition of the meconium microbiota. The cohort study pointed to a low-biomass microbiota consisting of the phyla Firmicutes, Proteobacteria and Actinobacteriota and the genera Staphylococcus, Escherichia-Shigella and Lactobacillus, and indicated that immediate perinatal factors affected the composition of the meconium microbiota more than did prenatal factors. CONCLUSIONS This finding supports the idea that the meconium microbiota mostly starts developing during delivery. IMPACT It is unclear when the first-pass meconium microbiota develops, and what are the sources of the colonization. In this systematic review, we found 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition relative to subsequent health of infants, but there was no consensus on the factors affecting the meconium microbiota development. In this cohort study, immediate perinatal factors markedly affected the meconium microbiota development while prenatal factors had little effect on it. As the meconium microbiota composition was influenced by immediate perinatal factors, the present study supports the idea that the initial gut microbiota develops mainly during delivery.
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Affiliation(s)
- Jenni Turunen
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
- Biocenter Oulu, University of Oulu, Oulu, Finland.
| | - Mysore V Tejesvi
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland
| | - Niko Paalanne
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Tytti Pokka
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Research Service Unit, Oulu University Hospital, Oulu, Finland
| | - Sajeen Bahadur Amatya
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Surbhi Mishra
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Anna Kaisanlahti
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Justus Reunanen
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Terhi Tapiainen
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
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Tilves C, Zhao HJ, Differding MK, Zhang M, Liu T, Hoyo C, Østbye T, Benjamin-Neelon SE, Mueller NT. Associations of Plastic Bottle Exposure with Infant Growth, Fecal Microbiota, and Short-Chain Fatty Acids. Microorganisms 2023; 11:2924. [PMID: 38138068 PMCID: PMC10745781 DOI: 10.3390/microorganisms11122924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 11/23/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND/OBJECTIVES Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. SUBJECTS/METHODS In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). RESULTS At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = -0.45, 95% CI: -0.76, -0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: -0.59, 95% CI: -0.99, -0.20) and lower isovaleric acid concentration at 3 months (mean difference: -2.12 μmol/g, 95% CI: -3.64, -0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. CONCLUSIONS Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.
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Affiliation(s)
- Curtis Tilves
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Heather Jianbo Zhao
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
- Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5T 3M7, Canada
| | - Moira K. Differding
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
| | - Mingyu Zhang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
- Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA 02215, USA
| | - Tiange Liu
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
| | - Cathrine Hoyo
- Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA;
| | - Truls Østbye
- Department of Family Medicine and Community Health, Duke University, Durham, NC 27708, USA;
| | - Sara E. Benjamin-Neelon
- Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Noel T. Mueller
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; (C.T.); (H.J.Z.); (M.K.D.); (M.Z.); (T.L.)
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Department of Pediatrics Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Human Milk Microbiome and Microbiome-Related Products: Potential Modulators of Infant Growth. Nutrients 2022; 14:nu14235148. [PMID: 36501178 PMCID: PMC9737635 DOI: 10.3390/nu14235148] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/25/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Infant growth trajectory may influence later-life obesity. Human milk provides a wide range of nutritional and bioactive components that are vital for infant growth. Compared to formula-fed infants, breastfed infants are less likely to develop later-onset obesity, highlighting the potential role of bioactive components present in human milk. Components of particular interest are the human milk microbiota, human milk oligosaccharides (HMOs), short-chain fatty acids (SCFAs), and antimicrobial proteins, each of which influence the infant gut microbiome, which in turn has been associated with infant body composition. SCFAs and antimicrobial proteins from human milk may also systemically influence infant metabolism. Although inconsistent, multiple studies have reported associations between HMOs and infant growth, while studies on other bioactive components in relation to infant growth are sparse. Moreover, these microbiome-related components may interact with each other within the mammary gland. Here, we review the evidence around the impact of human milk microbes, HMOs, SCFAs, and antimicrobial proteins on infant growth. Breastfeeding is a unique window of opportunity to promote optimal infant growth, with aberrant growth trajectories potentially creating short- and long-term public health burdens. Therefore, it is important to understand how bioactive components of human milk influence infant growth.
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Associations of maternal prenatal emotional symptoms with neurodevelopment of children and the neonatal meconium microbiota: A prospective cohort study. Psychoneuroendocrinology 2022; 142:105787. [PMID: 35512557 DOI: 10.1016/j.psyneuen.2022.105787] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/26/2022] [Accepted: 04/26/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship. METHODS A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287). RESULTS Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior. CONCLUSIONS Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.
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Saeed NK, Al-Beltagi M, Bediwy AS, El-Sawaf Y, Toema O. Gut microbiota in various childhood disorders: Implication and indications. World J Gastroenterol 2022; 28:1875-1901. [PMID: 35664966 PMCID: PMC9150060 DOI: 10.3748/wjg.v28.i18.1875] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/08/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.
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Affiliation(s)
- Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Manama 12, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
| | - Mohammed Al-Beltagi
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Yasser El-Sawaf
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Gastroenterology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al-Habib Medical Group, Manama 26671, Bahrain
| | - Osama Toema
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
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11
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Kielenniva K, Ainonen S, Vänni P, Paalanne N, Renko M, Salo J, Tejesvi MV, Pokka T, Pirttilä AM, Tapiainen T. Microbiota of the first-pass meconium and subsequent atopic and allergic disorders in children. Clin Exp Allergy 2022; 52:684-696. [PMID: 35212058 PMCID: PMC9314137 DOI: 10.1111/cea.14117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 01/28/2022] [Accepted: 02/07/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first-pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development. OBJECTIVE We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age. METHODS Prospective birth cohort study. Bacterial composition of first-pass meconium was analysed using bacterial 16S rRNA gene amplicon sequencing. Atopic and allergic diseases were evaluated via online survey or telephone to age 4 years, based on the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS During a 6-week period in 2014, 312 children were born at the Central Finland Central Hospital. Meconium was collected from 212 at a mean of 8-hour age. Outcome data at 4 years were available for 177 (83%) children, and 159 of these had sufficient amplification of bacterial DNA in meconium. Meconium microbiota composition, including diversity indices and relative abundances of the main phyla and genera, was not associated with subsequent atopic eczema, wheezing or cow's milk allergy. Principal components analysis did not identify any clustering of the meconium microbiomes of children with respect to wheezing or cow's milk allergy. CONCLUSIONS We found no evidence that gut microbiota composition of first-pass meconium is associated with atopic manifestations to age 4 years. However, larger studies are needed to fully exclude a relationship.
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Affiliation(s)
- Katja Kielenniva
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Sofia Ainonen
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Petri Vänni
- Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland.,Genobiomics Ltd., Oulu, Finland
| | - Niko Paalanne
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Marjo Renko
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics, University of Eastern Finland, Kuopio, Finland
| | - Jarmo Salo
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Mysore V Tejesvi
- Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland.,Genobiomics Ltd., Oulu, Finland
| | - Tytti Pokka
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | | | - Terhi Tapiainen
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland.,Biocenter Oulu, University of Oulu, Oulu, Finland
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12
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Kwak JH, Lee SW, Lee JE, Ha EK, Baek HS, Lee E, Kim JH, Han MY. Association of Antibiotic Use during the First 6 Months of Life with Body Mass of Children. Antibiotics (Basel) 2022; 11:antibiotics11040507. [PMID: 35453258 PMCID: PMC9033100 DOI: 10.3390/antibiotics11040507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/01/2022] [Accepted: 04/05/2022] [Indexed: 01/30/2023] Open
Abstract
In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children’s height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted β = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children.
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Affiliation(s)
- Ji Hee Kwak
- Department of Pediatrics, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Korea;
| | - Seung Won Lee
- Department of Data Science, College of Software Convergence, Sejong University, Seoul 05006, Korea; (S.W.L.); (J.E.L.)
- School of Medicine, Sungkyunkwan University, Suwon 16419, Korea
| | - Jung Eun Lee
- Department of Data Science, College of Software Convergence, Sejong University, Seoul 05006, Korea; (S.W.L.); (J.E.L.)
| | - Eun Kyo Ha
- Department of Pediatrics, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Seoul 07441, Korea;
| | - Hey-Sung Baek
- Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Seoul 05355, Korea;
| | - Eun Lee
- Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Korea;
| | - Ju Hee Kim
- Department of Data Science, College of Software Convergence, Sejong University, Seoul 05006, Korea; (S.W.L.); (J.E.L.)
- Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Seoul 05355, Korea;
- Correspondence: (J.H.K.); (M.Y.H.); Tel.: +82-2-2224-2251 (J.H.K.); +82-31-780-3491 (M.Y.H.); Fax: +82-31-780-3942 (M.Y.H.)
| | - Man Yong Han
- Department of Pediatrics, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea
- Correspondence: (J.H.K.); (M.Y.H.); Tel.: +82-2-2224-2251 (J.H.K.); +82-31-780-3491 (M.Y.H.); Fax: +82-31-780-3942 (M.Y.H.)
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13
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de Cuevillas B, Milagro FI, Tur JA, Gil-Campos M, de Miguel-Etayo P, Martínez JA, Navas-Carretero S. Fecal microbiota relationships with childhood obesity: A scoping comprehensive review. Obes Rev 2022; 23 Suppl 1:e13394. [PMID: 34913242 DOI: 10.1111/obr.13394] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 10/28/2021] [Indexed: 12/18/2022]
Abstract
Childhood obesity is a costly burden in most regions with relevant and adverse long-term health consequences in adult life. Several studies have associated excessive body weight with a specific profile of gut microbiota. Different factors related to fecal microorganism abundance seem to contribute to childhood obesity, such as gestational weight gain, perinatal diet, antibiotic administration to the mother and/or child, birth delivery, and feeding patterns, among others. This review reports and discusses diverse factors that affect the infant intestinal microbiota with putative or possible implications on the increase of the obesity childhood rates as well as microbiota shifts associated with excessive body weight in children.
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Affiliation(s)
- Begoña de Cuevillas
- Center for Nutrition Research, Department of Nutrition, Food Sciences and Physiology. School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain
| | - Fermín I Milagro
- Center for Nutrition Research, Department of Nutrition, Food Sciences and Physiology. School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- IdiSNA, Health Research Institute of Navarra, Pamplona, Spain
| | - Josep A Tur
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS & IDISBA, Palma de Mallorca, Spain
| | - Mercedes Gil-Campos
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Metabolism and Investigation Unit, Reina Sofia University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain
| | - Pilar de Miguel-Etayo
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Growth, Exercise, Nutrition and Development (GENUD) Research Group, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza. Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
| | - J Alfredo Martínez
- Center for Nutrition Research, Department of Nutrition, Food Sciences and Physiology. School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- IdiSNA, Health Research Institute of Navarra, Pamplona, Spain
- Precision Nutrition Program, Research Institute on Food and Health Sciences IMDEA Food. CSIC-UAM, Madrid, Spain
| | - Santiago Navas-Carretero
- Center for Nutrition Research, Department of Nutrition, Food Sciences and Physiology. School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- IdiSNA, Health Research Institute of Navarra, Pamplona, Spain
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14
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Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice. Cell Rep Med 2021; 2:100447. [PMID: 34841294 PMCID: PMC8606908 DOI: 10.1016/j.xcrm.2021.100447] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 06/17/2021] [Accepted: 10/19/2021] [Indexed: 12/13/2022]
Abstract
Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32–37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.
Very preterm neonates exhibit a distinct meconium microbiota composition Human meconium microbiota is transplanted to germ-free mice in this study Preterm transplant induces growth restriction, inflammation, and altered metabolism Initial gut microbiota may be causally related to complications of prematurity
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15
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Liu W, Fang X, Zhou Y, Dou L, Dou T. Machine learning-based investigation of the relationship between gut microbiome and obesity status. Microbes Infect 2021; 24:104892. [PMID: 34678464 DOI: 10.1016/j.micinf.2021.104892] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 09/30/2021] [Accepted: 10/10/2021] [Indexed: 02/06/2023]
Abstract
Gut microbiota is believed to play a crucial role in obesity. However, the consistent findings among published studies regarding microbiome-obesity interaction are relatively rare, and one of the underlying causes could be the limited sample size of cohort studies. In order to identify gut microbiota changes between normal-weight individuals and obese individuals, fecal samples along with phenotype information from 2262 Chinese individuals were collected and analyzed. Compared with normal-weight individuals, the obese individuals exhibit lower diversity of species and higher diversity of metabolic pathways. In addition, various machine learning models were employed to quantify the relationship between obesity status and Body mass index (BMI) values, of which support vector machine model achieves best performance with 0.716 classification accuracy and 0.485 R2 score. In addition to two well-established obesity-associated species, three species that have potential to be obesity-related biomarkers, including Bacteroides caccae, Odoribacter splanchnicus and Roseburia hominis were identified. Further analyses of functional pathways also reveal some enriched pathways in obese individuals. Collectively, our data demonstrates tight relationship between obesity and gut microbiota in a large-scale Chinese population. These findings may provide potential targets for the prevention and treatment of obesity.
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Affiliation(s)
- Wanjun Liu
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China; Department of Scientific Research, KMHD, Shenzhen 518126, China
| | - Xiaojie Fang
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China
| | - Yong Zhou
- Department of Scientific Research, KMHD, Shenzhen 518126, China
| | - Lihong Dou
- The First People's Hospital of Jiashan, Zhejiang 314100, China
| | - Tongyi Dou
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China.
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16
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Turunen J, Tejesvi MV, Paalanne N, Hekkala J, Lindgren O, Kaakinen M, Pokka T, Kaisanlahti A, Reunanen J, Tapiainen T. Presence of distinctive microbiome in the first-pass meconium of newborn infants. Sci Rep 2021; 11:19449. [PMID: 34593932 PMCID: PMC8484610 DOI: 10.1038/s41598-021-98951-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 09/14/2021] [Indexed: 01/04/2023] Open
Abstract
We critically evaluated the fetal microbiome concept in 44 neonates with placenta, amniotic fluid, and first-pass meconium samples. Placental histology showed no signs of inflammation. Meconium samples were more often bacterial culture positive after vaginal delivery. In next-generation sequencing of the bacterial 16S gene, before and after removal of extracellular and PCR contaminant DNA, the median number of reads was low in placenta (48) and amniotic fluid (46) and high in meconium samples (14,556 C-section, 24,860 vaginal). In electron microscopy, meconium samples showed extracellular vesicles. Utilizing the analysis of composition of microbiomes (ANCOM) against water, meconium samples had a higher relative abundance of Firmicutes, Lactobacillus, Streptococcus, and Escherichia-Shigella. Our results did not support the existence of the placenta and amniotic fluid microbiota in healthy pregnancies. The first-pass meconium samples, formed in utero, appeared to harbor a microbiome that may be explained by perinatal colonization or intrauterine colonization via bacterial extracellular vesicles.
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Affiliation(s)
- Jenni Turunen
- Medical Research Center and PEDEGO Research Unit, University of Oulu, Oulu, Finland. .,Biocenter Oulu, University of Oulu, Oulu, Finland.
| | - Mysore V Tejesvi
- Biocenter Oulu, University of Oulu, Oulu, Finland.,Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland
| | - Niko Paalanne
- Medical Research Center and PEDEGO Research Unit, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Jenni Hekkala
- Biocenter Oulu, University of Oulu, Oulu, Finland.,Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Outi Lindgren
- Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital, Oulu, Finland
| | | | - Tytti Pokka
- Medical Research Center and PEDEGO Research Unit, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Anna Kaisanlahti
- Biocenter Oulu, University of Oulu, Oulu, Finland.,Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Justus Reunanen
- Biocenter Oulu, University of Oulu, Oulu, Finland.,Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Terhi Tapiainen
- Medical Research Center and PEDEGO Research Unit, University of Oulu, Oulu, Finland.,Biocenter Oulu, University of Oulu, Oulu, Finland.,Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
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17
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Vänni P, Tejesvi MV, Ainonen S, Renko M, Korpela K, Salo J, Paalanne N, Tapiainen T. Delivery mode and perinatal antibiotics influence the predicted metabolic pathways of the gut microbiome. Sci Rep 2021; 11:17483. [PMID: 34471207 PMCID: PMC8410856 DOI: 10.1038/s41598-021-97007-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 08/17/2021] [Indexed: 12/13/2022] Open
Abstract
Delivery mode and perinatal antibiotics influence gut microbiome composition in children. Most microbiome studies have used the sequencing of the bacterial 16S marker gene but have not reported the metabolic function of the gut microbiome, which may mediate biological effects on the host. Here, we used the PICRUSt2 bioinformatics tool to predict the functional profiles of the gut microbiome based on 16S sequencing in two child cohorts. Both Caesarean section and perinatal antibiotics markedly influenced the functional profiles of the gut microbiome at the age of 1 year. In machine learning analysis, bacterial fatty acid, phospholipid, and biotin biosynthesis were the most important pathways that differed according to delivery mode. Proteinogenic amino acid biosynthesis, carbohydrate degradation, pyrimidine deoxyribonucleotide and biotin biosynthesis were the most important pathways differing according to antibiotic exposure. Our study shows that both Caesarean section and perinatal antibiotics markedly influence the predicted metabolic profiles of the gut microbiome at the age of 1 year.
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Affiliation(s)
- Petri Vänni
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.
| | - Mysore V Tejesvi
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
- Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland
| | - Sofia Ainonen
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
| | - Marjo Renko
- Department of Paediatrics, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Katja Korpela
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
| | - Jarmo Salo
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Niko Paalanne
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Terhi Tapiainen
- PEDEGO (Pediatrics, Dermatology, Gynecology, Obstetrics) Research Unit and Medical Research Center Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
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18
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Levels of Predominant Intestinal Microorganisms in 1 Month-Old Full-Term Babies and Weight Gain during the First Year of Life. Nutrients 2021; 13:nu13072412. [PMID: 34371922 PMCID: PMC8308764 DOI: 10.3390/nu13072412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/07/2021] [Accepted: 07/13/2021] [Indexed: 12/14/2022] Open
Abstract
The early life gut microbiota has been reported to be involved in neonatal weight gain and later infant growth. Therefore, this early microbiota may constitute a target for the promotion of healthy neonatal growth and development with potential consequences for later life. Unfortunately, we are still far from understanding the association between neonatal microbiota and weight gain and growth. In this context, we evaluated the relationship between early microbiota and weight in a cohort of full-term infants. The absolute levels of specific fecal microorganisms were determined in 88 vaginally delivered and 36 C-section-delivered full-term newborns at 1 month of age and their growth up to 12 months of age. We observed statistically significant associations between the levels of some early life gut microbes and infant weight gain during the first year of life. Classifying the infants into tertiles according to their Staphylococcus levels at 1 month of age allowed us to observe a significantly lower weight at 12 months of life in the C-section-delivered infants from the highest tertile. Univariate and multivariate models pointed out associations between the levels of some fecal microorganisms at 1 month of age and weight gain at 6 and 12 months. Interestingly, these associations were different in vaginally and C-section-delivered babies. A significant direct association between Staphylococcus and weight gain at 1 month of life was observed in vaginally delivered babies, whereas in C-section-delivered infants, lower Bacteroides levels at 1 month were associated with higher later weight gain (at 6 and 12 months). Our results indicate an association between the gut microbiota and weight gain in early life and highlight potential microbial predictors for later weight gain.
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19
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Jian C, Carpén N, Helve O, de Vos WM, Korpela K, Salonen A. Early-life gut microbiota and its connection to metabolic health in children: Perspective on ecological drivers and need for quantitative approach. EBioMedicine 2021; 69:103475. [PMID: 34256346 PMCID: PMC8324810 DOI: 10.1016/j.ebiom.2021.103475] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/18/2021] [Accepted: 06/18/2021] [Indexed: 12/15/2022] Open
Abstract
The colonisation and development of the gut microbiota has been implicated in paediatric metabolic disorders via its powerful effect on host metabolic and immune homeostasis. Here we summarise the evidence from human studies on the early gut microbiota and paediatric overweight and obesity. Manipulation of the early gut microbiota may represent a promising target for countering the burgeoning metabolic disorders in the paediatric population, provided the assembly patterns of microbiota and their health consequences can be decoded. Therefore, in this review, we pay particular attention to the important ecological drivers affecting the community dynamics of the early gut microbiota. We then discuss the knowledge gaps in commonly studied exposures linking the gut microbiota to metabolic disorders, especially regarding maternal factors and antibiotic use. This review also attempts to give directions for future studies aiming to identify predictive and corrective measures for paediatric metabolic disorders based on the gut microbiota. Gut microbiota; Metabolism; Paediatric overweight and obesity; Ecological driver; Dynamics; Infants.
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Affiliation(s)
- Ching Jian
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Noora Carpén
- Children's Hospital, Pediatric Research Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Otto Helve
- Children's Hospital, Pediatric Research Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Finnish Institute for Health and Welfare, Department of Health Security, Helsinki, Finland
| | - Willem M de Vos
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Katri Korpela
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Anne Salonen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
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20
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Berry ASF, Pierdon MK, Misic AM, Sullivan MC, O’Brien K, Chen Y, Murray SJ, Ramharack LA, Baldassano RN, Parsons TD, Beiting DP. Remodeling of the maternal gut microbiome during pregnancy is shaped by parity. MICROBIOME 2021; 9:146. [PMID: 34176489 PMCID: PMC8237508 DOI: 10.1186/s40168-021-01089-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 05/06/2021] [Indexed: 05/09/2023]
Abstract
BACKGROUND The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies-referred to as maternal parity-as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans. RESULTS Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring "quadrads"-each consisting of one mother sow and three piglets-linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth. CONCLUSIONS Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants. Video abstract.
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Affiliation(s)
- Alexander S. F. Berry
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 USA
| | - Meghann K. Pierdon
- Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Ana M. Misic
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Megan C. Sullivan
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Kevin O’Brien
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Ying Chen
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Samuel J. Murray
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Lydia A. Ramharack
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Robert N. Baldassano
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 USA
| | - Thomas D. Parsons
- Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
| | - Daniel P. Beiting
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA USA
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21
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LeCroy MN, Kim RS, Stevens J, Hanna DB, Isasi CR. Identifying Key Determinants of Childhood Obesity: A Narrative Review of Machine Learning Studies. Child Obes 2021; 17:153-159. [PMID: 33661719 PMCID: PMC8418446 DOI: 10.1089/chi.2020.0324] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Machine learning is a class of algorithms able to handle a large number of predictors with potentially nonlinear relationships. By applying machine learning to obesity, researchers can examine how risk factors across multiple settings (e.g., school and home) interact to best predict childhood obesity risk. In this narrative review, we provide an overview of studies that have applied machine learning to predict childhood obesity using a combination of sociodemographic and behavioral risk factors. The objective is to summarize the key determinants of obesity identified in existing machine learning studies and highlight opportunities for future machine learning applications in the field. Of 15 peer-reviewed studies, approximately half examined early childhood (0-24 months of age) determinants. These studies identified child's weight history (e.g., history of overweight/obesity or large increases in weight-related measures between birth and 24 months of age) and parental overweight/obesity (current or prior) as key risk factors, whereas the remaining studies indicated that social factors and physical inactivity were important in middle childhood and late childhood/adolescence. Across age groups, findings suggested that race/ethnic-specific models may be needed to accurately predict obesity from middle childhood onward. Future studies should consider using existing large data sets to take advantage of the benefits of machine learning and should collect a wider range of novel risk factors (e.g., psychosocial and sociocultural determinants of health) to better predict childhood obesity. Ultimately, such research can aid in the development of effective obesity prevention interventions, particularly ones that address the disproportionate burden of obesity experienced by racial/ethnic minorities.
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Affiliation(s)
- Madison N. LeCroy
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.,Address correspondence to: Madison N. LeCroy, PhD, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
| | - Ryung S. Kim
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - June Stevens
- Department of Nutrition and Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - David B. Hanna
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Carmen R. Isasi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
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22
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Alderete TL, Jones RB, Shaffer JP, Holzhausen EA, Patterson WB, Kazemian E, Chatzi L, Knight R, Plows JF, Berger PK, Goran MI. Early life gut microbiota is associated with rapid infant growth in Hispanics from Southern California. Gut Microbes 2021; 13:1961203. [PMID: 34424832 PMCID: PMC8386720 DOI: 10.1080/19490976.2021.1961203] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/06/2021] [Accepted: 07/20/2021] [Indexed: 02/04/2023] Open
Abstract
We aimed to determine if the newborn gut microbiota is an underlying determinant of early life growth trajectories. 132 Hispanic infants were recruited at 1-month postpartum. The infant gut microbiome was characterized using 16S rRNA amplicon sequencing. Rapid infant growth was defined as a weight-for-age z-score (WAZ) change greater than 0.67 between birth and 12-months of age. Measures of infant growth included change in WAZ, weight-for-length z-score (WLZ), and body mass index (BMI) z-scores from birth to 12-months and infant anthropometrics at 12-months (weight, skinfold thickness). Of the 132 infants, 40% had rapid growth in the first year of life. Multiple metrics of alpha-diversity predicted rapid infant growth, including a higher Shannon diversity (OR = 1.83; 95% CI: 1.07-3.29; p = .03), Faith's phylogenic diversity (OR = 1.41, 95% CI: 1.05-1.94; p = .03), and richness (OR = 1.04, 95% CI: 1.01-1.08; p = .02). Many of these alpha-diversity metrics were also positively associated with increases in WAZ, WLZ, and BMI z-scores from birth to 12-months (pall<0.05). Importantly, we identified subsets of microbial consortia whose abundance were correlated with these same measures of infant growth. We also found that rapid growers were enriched in multiple taxa belonging to genera such as Acinetobacter, Collinsella, Enterococcus, Neisseria, and Parabacteroides. Moreover, measures of the newborn gut microbiota explained up to an additional 5% of the variance in rapid growth beyond known clinical predictors (R2 = 0.37 vs. 0.32, p < .01). These findings indicate that a more mature gut microbiota, characterized by increased alpha-diversity, at as early as 1-month of age, may influence infant growth trajectories in the first year of life.
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Affiliation(s)
- Tanya L. Alderete
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA
| | - Roshonda B. Jones
- Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Justin P. Shaffer
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | | | - William B. Patterson
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA
| | - Elham Kazemian
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA
| | - Lida Chatzi
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Jasmine F. Plows
- Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Paige K. Berger
- Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Michael I. Goran
- Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
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